Recently, resonant infrared-pulsed laser deposition (PLD) of a variety of polymers has been successfully demonstrated. This technique has been applied with promising results to processing polymer ...materials that previously resulted in significant polymer decomposition under other wavelength processing conditions.
Aspects of between-individual trophic niche width can be explored through the isotopic niche concept. In many cases isotopic variability can be influenced by the scale of sampling and biological ...characteristics including body size or sex. Sample size-corrected (SEAc) and Bayesian (SEAb) standard ellipse areas and generalised least squares (GLS) models were used to explore the spatial variability of δ13C and δ15N in Kiwa tyleri (decapod), Gigantopelta chessoia (peltospirid gastropod) and Vulcanolepas scotiaensis (stalked barnacle) collected from 3 hydrothermal vent field sites (E2, E9N and E9S) on the East Scotia Ridge (ESR), Southern Ocean. SEAb only revealed spatial differences in isotopic niche area in male K. tyleri. However, the parameters used to draw the SEAc, eccentricity (E) and angle of the major SEAc axis to the x-axis (θ), indicated spatial differences in the relationships between δ13C and δ15N in all 3 species. The GLS models indicated that there were spatial differences in isotope–length trends, which were related to E and θ of the SEAc. This indicated that E and θ were potentially driven by underlying trophic and biological processes that varied with body size. Examination of the isotopic niches using standard ellipse areas and their parameters in conjunction with length-based analyses provided a means by which a proportion of the isotopic variability within each species could be described. We suggest that the parameters E and θ offer additional ecological insight that has so far been overlooked in isotopic niche studies.
Summary Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society ...produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients.
Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and ...early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2month-old) and older (6.5month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring.
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► In utero exposure to 300mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.
Non‐alcohol‐induced steatohepatitis (NASH) is characterized by elevated serum aminotransferase activities with hepatic steatosis, inflammation, and occasionally fibrosis that may progress to ...cirrhosis. No established treatment exists for this potentially serious disorder. Our aim was to conduct a pilot study to evaluate the safety and estimate the efficacy of ursodeoxycholic acid (UDCA) and clofibrate in the treatment of NASH. Forty patients were diagnosed with NASH based on a compatible liver biopsy with other causes of liver disease, including alcohol abuse, excluded by history, serum tests, and use of ultrasound. Twenty‐four patients received 13 to 15 mg/kg/d of UDCA for 12 months. Sixteen patients with hypertriglyceridemia were placed on clofibrate, 2 g/day for 12 months. Twenty‐five women and 15 men entered the study. Six of 40 patients (15%) withdrew because of side effects. Four additional patients were withdrawn because of noncompliance; one of them later required liver transplantation. In the UDCA group, the decreases in mean serum levels of alkaline phosphatase, alanine transaminase (ALT), and γ‐glutamyl transpeptidase (GGT) as well as histological grade of steatosis were significant. Among the patients treated with clofibrate, no change from baseline was found in mean ALT, aspartate transaminase (AST), GGT, bilirubin, triglycerides, and cholesterol, or in histological grade of steatosis, inflammation, or fibrosis after 12 months of treatment as compared with entry. Alkaline phosphatase activities decreased significantly from baseline. Despite the known lipid‐lowering effects of clofibrate, it did not appear to be of clinical benefit in the treatment of NASH in this 1‐year pilot study. However, treatment of NASH with UDCA for 12 months resulted in significant improvement in alkaline phosphatase, ALT, GGT, and hepatic steatosis. The possible benefit of UDCA therapy should be further investigated in the context of a randomized, controlled trial.
Two techniques, Matrix-Assisted Pulsed-Laser Evaporation (MAPLE) and MAPLE Direct Write (MDW) were developed to deposit biomaterial thin-films. MAPLE involves dissolving or suspending the biomaterial ...in a volatile solvent, freezing the mixture to create a solid target, and using a low fluence pulsed laser to evaporate the target for deposition of the solute inside a vacuum system. Using simple shadow masks, i.e. lines, dots and arrays, pattern features with length scales as small as 20 μm can be deposited using multiple materials on different types of substrates. MDW uses pulsed laser to directly transfer material from a ribbon to a substrate. Patterns with a spatial resolution of ∼10 μm can be written directly. Biomaterials ranging from polyethylene glycol to eukaryotic cells, i.e. Chinese hamster ovaries, were deposited with no measurable damage to their structures or genotype. Deposits of immobilized horseradish peroxidase, an enzyme, in the form of a polymer composite with a protective coating, i.e. polyurethane, retained their enzymatic functions. A dopamine electrochemical sensor was fabricated by MDW using a natural tissues/graphite composite. These examples and the unique features of MAPLE and MDW for biosensor fabrication have been discussed.
This paper reports the deposition of active protein thin films by a novel laser-based approach termed matrix-assisted pulsed laser evaporation (MAPLE). We have deposited uniform 10 nm to nearly 1 μm ...thin films of insulin and horseradish peroxidase (HRP). We performed several experiments to characterize the chemical integrity of the deposited films. Matrix assisted laser desorption/ionization and liquid chromatography/electrospray ionization mass spectrometry experiments performed on MAPLE-deposited insulin films indicate that the laser−material interaction involved in this deposition technique does not modify the protein's mass. Fourier transform infrared spectroscopy experiments show that the chemical functionality and secondary structure of MAPLE-deposited HRP are nearly identical to those of the native protein. We also find that deposited HRP films retain their ability to catalyze the reduction of 3,3‘-diaminobenzidine (DAB), suggesting that the active site of transferred proteins is unaffected by the MAPLE process. We also produced patterns and multilayers with feature sizes from 20 to 250 μm by depositing different biomaterials through a shadow mask. Patterns of physisorbed HRP were then protected from dissolution in an aqueous environment by a semipermeable polymer overlayer that was deposited in situ using pulsed laser deposition. This polymer membrane protects the protein pattern when it is exposed to DAB solution and enables the optical observation of HRP activity for spots as small as 2000 μm2. These results demonstrate that MAPLE is a preferred technique for depositing active biomolecules for applications ranging from microfluidic sensor devices to gene and protein recognition microarrays.
The risk of complications from percutaneous liver biopsy is low, but discomfort is common and complications require hospitalization in approximately 4% of patients. The optimal method of performing ...these biopsies is unknown. The goal of our study was to determine whether the use of ultrasonography in the biopsy room immediately prior to or during the procedure would lessen the risk of complications and to compare the safety and efficacy in obtaining tissue by use of a Trucut needle versus an automatic biopsy needle. Between 1992 and 1994, 836 patients were entered into a randomized study (489 in Rochester, MN; 347 in Barcelona, Spain). Patients were randomized immediately prior to liver biopsy into four groups: Trucut needle, or automatic biopsy needle, and with or without ultrasonography. Fisher's Exact Test and a logistic regression model were also used to assess the effect of needle and ultrasonography on the odds for complications. The four biopsy groups were well‐matched at entry with respect to age, sex, underlying liver disease, hemoglobin, prothrombin time, and platelet count. The use of ultrasound was associated with a decreased rate of hospitalization for pain, hypotension, or bleeding (2 vs. 9, P < .05). No difference in safety was found between the two types of needles. The number of passes needed to obtain specimens was similar for all four groups. The average length of the specimen was slightly greater with ultrasonographic‐guided biopsies (1.7 mm vs. 1.6 mm, P < .05) and with biopsies obtained using the automatic biopsy needle when compared with the Trucut needle (1.7 mm vs. 1.5 mm, P < .05), but this did not seem to be clinically important. The addition of ultrasonography reduces complications in patients undergoing percutaneous liver biopsy. The type of needle appears to offer little difference in safety or yield of diagnostic tissue. The use of ultrasonography for guidance of percutaneous liver biopsy will lead to a lower rate of complications. The value of this benefit must be weighed against the added cost of ultrasonographic guidance.
Background Although assessment of cardiovascular safety is mandated by regulatory agencies for the development of new drugs to treat type 2 diabetes, evaluation of their renal safety has been ...relatively neglected. Study Design Individual patient–level data pooled analysis of 13 phase 2 or 3 randomized, double-blind, placebo-controlled, clinical trials of the dipeptidyl peptidase 4 inhibitor linagliptin. Setting & Participants Participants who participated in any of 13 randomized clinical trials and fulfilled predefined inclusion/exclusion criteria, such as being drug-naive (hemoglobin A1c , 7.0%-11.0% 53-97 mmol/mol) or being on background glucose-lowering therapy (hemoglobin A1c , 6.5%-10.5% 48-91 mmol/mol). Intervention Of 5,466 consenting individuals with inadequately controlled type 2 diabetes, 3,505 received linagliptin, 5 mg/d, and 1,961 received placebo. Outcomes The primary kidney disease outcome was defined as first occurrence during the study of 6 predefined safety end points: new onset of moderate elevation of albuminuria (urinary albumin-creatinine ratio ACR >30 mg/g with baseline values ≤ 30 mg/g), new onset of severe elevation of albuminuria (ACR > 300 mg/g with baseline values ≤ 300 mg/g), reduction in kidney function (serum creatinine increase to ≥250 μmol/L from a baseline value < 250 μmol/L), halving of estimated glomerular filtration rate (loss of baseline eGFR > 50%), acute renal failure (ascertained from diagnostic codes), or death from any cause. Measurements Albuminuria was assessed using ACR. GFR was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Results Cumulative exposure (person-years) was 1,751 for linagliptin and 1,055 for placebo. The primary composite outcome occurred in 448 (12.8%) and 306 (15.6%) participants in the linagliptin and placebo groups, respectively. Linagliptin treatment significantly reduced the hazard of kidney disease events by 16% compared with placebo (HR, 0.84; 95% CI, 0.72-0.97; P = 0.02). Limitations Retrospective and hypothesis-generating study involving short- to midterm clinical trials. Conclusions Linagliptin was not associated with increased kidney disease risk in patients with type 2 diabetes. The potential of this drug to improve kidney disease outcomes warrants further investigation.
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